Background
On average, KRAS is mutated in approximately 50% of patients with colorectal cancer.
Chemotherapy in combination with targeted drugs is standard of care option for patients with metastatic colorectal cancer with success rate of over 50% as the first line of treatment. In the second line, efficacy of chemotherapy and targeted drugs are much lower with success rate of 5% for FOLFIRI + Avastin. New treatment options are urgently needed in particular for the 50% of patients harboring a KRAS mutation.
Polo-Like Kinase1, PLK1, is a proven therapeutic target that is over-expressed in most cancers. Oral Onvansertib specifically inhibits PLK1 and by doing that, causes cell death.
About the study
To be eligible for enrollment on the trial, patients had to have metastatic and unresectable colorectal cancer, KRAS mutations in cancer cells, have progressed on or were intolerant to Oxaliplatin-based chemotherapy and who experienced disease progression on less than 6 months of first line therapy.
Patients had to be negative for BRAF V600E mutation and microsatellite instability high/deficient mismatch repair status.
In this phase 1b/2 study, the combination of Onvansertib with the current standard of care – FOLFIRI and Avastin – was found to have preliminary efficacy and favorable side effects when used as a second-line treatment for patients with KRAS-mutated metastatic colorectal cancer.
Study results
- 42% of patients achieved a reduction of metastases size. Moreover, 1 of these patients went on to receive curative surgery.
- 67% of patients experienced durable responses that ranged from 6 months to 13 months.
Side Effects
The most common side effects included neutropenia , fatigue and nausea. Most of these effects were very mild in severity.
Conclusions
The combination of Onvansertib with the current standard of care – FOLFIRI and Avastin – was found to have preliminary efficacy and favorable side effects when used as a second-line treatment for patients with KRAS-mutated metastatic colorectal cancer.
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